Complement Factor H(CFH) is a multifunctional protein that acts as a key regulator of the complement system. See Zipfel, 2001, “Factor H and disease: a complement regulator affects vital body functions” Semin Thromb Hemost. 27:191-9. The Factor H protein activities include: (I) binding to C-reactive protein (CRP), (2) binding to C3b, (3) binding to heparin, (4) binding to sialic acid; (5) binding to endothelial cell surfaces, (6) binding to cellular integrin receptors (7) binding to pathogens, including microbes (see FIG. 3 of U.S. patent publication No. 20070020647), and (8) C3b co-factor activity. The Factor H gene, known as HF1, CFH and HF, is located on human chromosome 1, at position 1q32. The 1q32 locus contains a number of complement pathway-associated genes. One group of these genes, referred to as the regulators of complement activation (RCA) gene cluster, contains the genes that encode Factor H, five Factor H-related proteins (FHR-1, FHR-2, FHR-3, FHR-4 and FHR-5 or CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5, respectively), and the gene encoding the beta subunit of coagulation factor XIII. The Factor H and Factor H related proteins are composed almost entirely of short consensus repeats (SCRs). Factor H and FHL1 are composed of SCRs 1-20 and 1-7, respectively. FHR-1, FHR-2, FHR-3, FHR-4 and FHR-5 are composed of 5, 4, 5, 5 and 8 SCRs, respectively. The order of genes, from centromere to telomere is FH/FHL1, FHR-3, FHR-1, FHR-4, FHR-2 and FHR-5.
Factor H Gene
The Factor H cDNA encodes a polypeptide 1231 amino acids in length having an apparent molecular weight of 155 kDa (see Ripoche et al., 1988, Biochem J 249:593-602). There is an alternatively spliced form of Factor H known as FHL-1 (and also has been referred to as HFL1 or CFHT). FHL-1 corresponds essentially to exons 1 through 9 of Factor H (see Ripoche et al., 1988, Biochem J 249:593-602). The FHL1 cDNA encodes a polypeptide 449 amino acids in length having an apparent molecular weight of 45-50 kDa. The first 445 amino acids of FH1 and FHL1 are identical, with FHL1 having four unique C-terminal amino acids (encoded by alternative exon 10A, which is located in the intron between exon 9 and exon 10. cDNA and amino acid sequence data for human Factor H and FHL1 are found in the EMBL/GenBank Data Libraries under accession numbers Y00716 and X07523, respectively. The 3926 base nucleotide sequence of the reference form of human Factor H cDNA has GenBank accession number Y00716 and the polypeptide has GenBank accession number Y00716. The 1658 base nucleotide sequence of the reference form of HFL1, the truncated form of the human Factor H, has GenBank accession number X07523, and the polypeptide sequence has GenBank accession number X07523. The Factor H gene sequence (150626 bases in length) has GenBank accession number AL049744. The Factor H promoter is located 5′ to the coding region of the Factor H gene.
FHR-1 Gene
The FHR-1 gene is also known as CFHR1, CFHL1, CFHL, FHR1 and HFL1. The FHR-1 cDNA encodes a polypeptide 330 amino acids in length having an predicted molecular weight of 39 kDa (see Estaller et al., 1991, J. Immunol. 146:3190-3196). cDNA and amino acid sequence data for human FHR-1 are found in the EMBL/GenBank Data Libraries under accession number M65292. The FHR-1 gene sequence is found under GenBank accession number AL049741.
FHR-2 Gene
The FHR-2 gene is also known as CFHR2, CFHL2, FHR2 and HFL3. The FHR-2 cDNA encodes a polypeptide 270 amino acids in length having a predicted molecular weight of 31 kDa (see Strausberg et al., Proc. Natl. Acad. Sci. USA 99:16899-16903). cDNA and amino acid sequence data for human FHR-2 are found in the EMBL/GenBank Data Libraries under accession number BC022283. The FHR-2 gene sequence is found under GenBank accession number AL139418.
FHR-3 Gene
The FHR-3 gene is also known as CFHR3, CFHL3, FHR3 and HLF4. The FHR-3 cDNA encodes a polypeptide 330 amino acids in length having a predicted molecular weight of 38 kDa (see Strausberg et al., Proc. Natl. Acad. Sci. USA 99:16899-16903). cDNA and amino acid sequence data for human FHR-3 are found in the EMBL/GenBank Data Libraries under accession number BC058009. The FHR-3 gene sequence is found under GenBank accession number AL049741.
FHR-4 Gene
The FHR-4 gene is also known as CFHR4, CFHL4 and FHR4. The FHR-4 cDNA encodes a polypeptide 331 amino acids in length having a predicted molecular weight of 38 kDa (see Skerka et al., 1991, J. Biol. Chem. 272:5627-5634). cDNA and amino acid sequence data for human FHR-4 are found in the EMBL/GenBank Data Libraries under accession number X98337. The FHR-4 gene sequence is found under GenBank accession numbers AF190816 (5′ end), AL139418 (3′ end) and BX248415.
FHR-5 Gene
The FHR-5 gene is also known as CFHR5, CFHL5 and FHR5. The CFHR5 cDNA encodes a polypeptide 569 amino acids in length having an apparent molecular weight of 65 kDa (see McRae et al., 2001, J. Biol. Chem. 276:6747-6754). cDNA and amino acid sequence data for human CFHR5 are found in the EMBL/GenBank Data Libraries under accession number AF295327. The 2821 base nucleotide sequence of the reference form of human CFHR5 has GenBank accession number AF295327, and the polypeptide sequence has GenBank accession number AAK15619. The CFHR5 genomic sequence is found under GenBank accession numbers AL139418 (5′ end) and AL353809 (3′ end). The FHR-5 promoter is located 5′ to the coding region of the CFHR5 gene.